Expression of the thioredoxin system in interstitial lung disease

The thioredoxin system containing thioredoxin (Trx) and thioredoxin reductase (TrxR) has profound effects on cell proliferation and protection against exogenous oxidants. The significance of the Trx system in human lung and lung diseases is, however, largely unresolved. Altogether, 66 specimens of human lung were investigated by immunohistochemistry for their expression of Trx and TrxR. The diseases included interstitial pneumonias such as usual interstitial pneumonia (UIP), desquamative interstitial pneumonia (DIP), and UIP associated with collagen vascular diseases (CVD-ILD), and granulomatous diseases such as sarcoidosis and allergic alveolitis. The ultrastructural localization of Trx and TrxR was analysed by immunoelectron microscopy. In healthy lung, Trx and TrxR were expressed in bronchial epithelium and alveolar macrophages. Trx and TrxR were highly concentrated in areas of metaplastic epithelium in UIP and in alveolar macrophages in DIP, though fibrotic areas in UIP were mainly negative. The expression of both enzymes was clearly weaker in CVD-ILD than in UIP. Granulomas of sarcoidosis showed moderate to intense Trx immunoreactivity. Ultrastructurally, Trx and TrxR were expressed diffusely in the cytosolic compartment and plasma membrane of metaplastic type II pneumocytes, macrophages, and bronchial epithelial cells. This study highlights the importance of Trx and TrxR in primary defence in bronchial epithelium, alveolar epithelium, and macrophages in human lung, but also indicates that elevated expression of these proteins may serve as markers of ongoing cell regeneration and inflammation.     

Maternal morbidity and perinatal outcomes among pregnant women with respiratory hospitalizations during influenza season

OBJECTIVES: A population-based assessment of maternal and perinatal morbidity related to respiratory illness during influenza season among pregnant women has not been published. The objectives of this investigation were to describe and quantify the impact of respiratory hospitalization during pregnancy on serious maternal and perinatal morbidity. STUDY DESIGN: A matched cohort study using an administrative database of pregnant women enrolled in the Tennessee Medicaid population to determine pregnancy outcomes associated with respiratory hospitalizations during influenza season. Pregnant women aged 15 to 44 years with a respiratory hospitalization during influenza seasons 1985-1993 were matched by gestational age and presence of comorbidity with pregnant control subjects without a respiratory hospitalization. RESULTS: During the eight influenza seasons studied, 293 women with singleton pregnancies had respiratory disease hospitalizations (5.1:1000). Women with asthma had high rates of such hospitalization (59.7:1000). Compared with matched controls, women with respiratory hospitalizations had similar modes of delivery, delivery length of stay, and episodes of preterm labor. The prevalence of prematurity and low birth weight among infants born to such women was likewise similar between the two groups. CONCLUSION: In this population of pregnant women, those with asthma accounted for half of all respiratory-related hospitalizations during influenza seasons, with 6% of pregnant women with asthma requiring respiratory hospitalization during influenza season, (odds ratio 10.63, 95% CI, 8.18-13.83, compared with women without a medical comorbidity). We detected no significant increase in adverse perinatal outcomes associated with respiratory hospitalizations during influenza season.     

Efficacy and safety of levofloxacin in the context of other contemporary fluoroquinolones: a review

Background

In recent years, fluoroquinolone research has focused on achieving several goals, including (1) enhanced potency against gram-positive cocci, notably Streptococcus pneumoniae, and anaerobes, while (2) maintaining potency against gram-negative pathogens, (3) optimizing pharmacokinetics and pharmacodynamics (PK/PD), and (4) minimizing potential adverse drug reactions through recognition and avoidance of structural configurations that have characterized earlier, reactive compounds.

Objective

This review examines the efficacy and safety of fluoroquinolones and the specific clinical evidence regarding levofloxacin.

Methods

Using published literature collected over time by the author, a review was conducted, focusing on the efficacy and safety profile of levofloxacin and other fluoroquinolones.

Results

The newer fluoroquinolones have fulfilled many of the research goals described above. Levofloxacin has improved anti-gram-positive potency, PK/PD properties, a proven clinical trial record (particularly for communityacquired pneumonia [CAP]), and an excellent safety profile—in the context of the treatment of >250 million patients worldwide in the past decade. It is licensed for management of drug-resistant S pneumoniae infections in the United States and has gained widespread formulary acceptance and guideline inclusion. Studies assessing levofloxacin for CAP therapy show significant advantages over standard therapy, such as trends toward reduced IV therapy and length of hospitalization, reduced mortality, and significant associated cost reduction. In addition, levofloxacin has proved highly effective in acute exacerbations of chronic bronchitis (AECB), with excellent clinical and bacteriologic results, typical of the class, and significant advantages—in terms of clinical response, overall pathogen eradication, extension of the symptom-free period, and trends toward a reduction in the number of consultation visits and hospitalizations—over standard agents, such as the oral cephalosporins.

Conclusions

Levofloxacin offers a combination of documented efficacy and tolerability, and provides an important option for the treatment of bacterial infections, including CAP and AECB, compared with standard agents used in the management of lower respiratory tract infections.     

Community-acquired pneumonia and do not resuscitate orders

OBJECTIVES: From a cohort of patients with community-acquired pneumonia (CAP) who required admission to hospital, to describe the subset of patients having a do not resuscitate (DNR) order and to compare them with those who did not have such an order. DESIGN: Retrospective subset analysis of data from the pneumonia patient outcomes research team study. SETTING: Three hospitals in the United States and one in Canada. PARTICIPANTS: Hospitalized patients aged 18 and older with CAP. MEASUREMENTS: Sociodemographic features, severity of illness, antibiotic therapy, length of stay, mortality, admission to special care units, and mortality attributable to pneumonia. RESULTS: The 199 (14.9) of 1,339 inpatients with CAP who had a DNR order written within 24 hours of admission and an additional 96 (7.2) patients who had such an order written later were compared with the 1,044 who never had a DNR order. The 199 patients with an initial DNR and 96 later DNR were older (median age 81 and 78 vs 65 years, respectively; P< .001), more likely to be white (92.5 and 90.6 vs 84.8; P = .007), and more likely to have come from a nursing home or chronic care facility (53.8 and 31.3 vs 4.5; P< .001). The two DNR groups received more antibiotics for a longer time than the never DNR patients. The DNR patients had longer lengths of stay than the never DNR patients (medians 9 and 12 vs 7 days). There were 89 in-hospital deaths among the 1,339 patients, but only 11 of these were among patients who did not have a DNR order during the first 30 days (sensitivity, specificity, and positive and negative predictive values of a DNR order for in-hospital mortality were 87.6, 82.6, 26.4, and 98.9, respectively). The 90-day mortality rates were 43.2 for the initial DNR group, 61.5 in the later DNR group, and 4.7 for the never DNR group (P< .001). Pneumonia-attributable mortality accounted for most of the in-hospital deaths but did not differ by DNR status. Only 31.7 of the initial DNR patients and 24.0 of the later DNR patients were discharged home, versus 82.6 of the other patients (P< .001). In a multivariate analysis, the following were predictive of initial DNR: age, nursing home care, active cancer, dementia, neuromuscular disorders, altered mental status, low systolic blood pressure, tachypnea, abnormal hematocrit, abnormal blood urea nitrogen, and absence of alcohol or intravenous drug abuse. In similar analyses of DNR at any time, additional predictors included aspiration, low white blood count, chronic pulmonary disease, cerebrovascular disease, and congestive heart failure. CONCLUSION: Most in-hospital pneumonia deaths occur in patients who have a DNR order. DNR orders written within 24 hours of admission primarily reflect comorbid status, whereas DNR orders written later during hospitalization reflect the futility of care plus comorbidity.     

Laryngotracheal separation for intractable aspiration pneumonia in neurologically impaired children: experience with 11 cases

Purpose

Laryngotracheal separation (LTS) with or without end-to-side laryngoesophagostomy was performed as an antiaspiration procedure for intractable aspiration pneumonia in 11 children. The effectiveness of LTS for preventing aspiration was investigated.

Methods

Eleven children aged from 9 months to 16 years with intractable aspiration pneumonia underwent LTS with (n = 8) or without (n = 3) laryngoesophagostomy at our institution over the last 2 years. Of these 11 patients, 7 underwent fundoplication with or without gastrostomy for gastroesophageal reflux (GER) before LTS (n = 5) or concurrently with LTS (n = 2). The effectiveness of LTS was evaluated by chart review and follow-up phone questionnaires.

Results

LTS decreased the frequency of performing suction from an average of once every 30 minutes to once every 4.5 hours in all patients. In 5 patients who underwent fundoplication with gastrostomy before LTS, aspiration pneumonia remained unless they underwent LTS. Two patients who underwent LTS with or without laryngoesophagostomy tolerated oral feeding postoperatively. All parents rated LTS as excellent or good in terms of improving the quality of life.

Conclusions

LTS can be recommended for neurologically impaired children with intractable aspiration as a primary surgical intervention. If patients show impaired swallowing and GER, LTS could be performed simultaneously with fundoplication and gastrostomy.     

Pneumocystis carinii pneumonia in HIV negative patients with primary brain tumors

Background: Pneumocystis carinii pneumonia (PCP) is an opportunistic infection with rather adverse outcomes. An unexpected increase in cases of PCP was noted in the brain tumor population at the Johns Hopkins Hospital (JHH) in 2000. This prompted the present review of the clinical features and risk factors for PCP in the human immunodeficiency virus (HIV) negative brain tumor population. Methods: The study was located at the JHH. A retrospective review of medical records was done to identify patients with discharge diagnosis of PCP from 1980 to 2001. Patients who were HIV positive were excluded. A detailed analysis was done of patients with brain tumors. Results: From 1980 to 2001, 468 cases of PCP were identified, diagnosed histologically or clinically, of which 110 were patients with an underlying malignancy. Of the 110 cases 15 were seen in the brain tumor population. Of these, 6 patients were seen in 2000 and one in early 2001. Three of these had primary central nervous system (CNS) lymphoma (PCNSL) on high dose methotrexate. Eight of the fifteen episodes (53.3%) were fatal despite institution of antibiotics and supportive therapy. Conclusion: The incidence and mortality due to Pneumocystis carinii among the brain tumor population is increasing. While corticosteroids are known immunosupressants, prescribing patterns for these medications has not changed lately. However, high dose methotrexate is now being used in PCNSL and could be a complicating factor. Since effective prophylaxis exists, it should be considered in patients with brain tumors receiving high dose steroids, high dose methotrexate or with lymphopenia.     

中西医结合治疗非典型肺炎103例临床观察

目的：观察中西医结合方法治疗非典型肺炎的疗效。方法：西医采用营养支持、呼吸机辅助通气、抗感染及糖皮质激素等方法治疗;中药根据中医辨证分期选方用药。统计学方法采用描述性分析法。结果：103中治愈96例(93．2％),死亡7例(6．8％);入院治疗后退热时间为(6．72±3．95)天;胸片复查病灶完全吸收94例,病灶吸收时间(18．13±8．99)天;2例胸片呈局部纤维索条样改变。结论：SARS属中医“温病”范畴,采用中西医结合治疗有积极作用。     

Sulfa resistance and dihydropteroate synthase mutants in recurrent Pneumocystis carinii pneumonia

Failure of sulfa or sulfone prophylaxis is associated with mutations in Pneumocystis carinii gene coding for dihydropteroate synthase (DHPS). The DHPS genotype was analyzed in AIDS patients who had two separate episodes of P. carinii pneumonia. The results suggest that DHPS mutations can be selected de novo within patients by the pressure of a sulfa or sulfone drug.     

Seasonal patterns of invasive pneumococcal disease

Pneumococcal infections increase each winter, a phenomenon that has not been well explained. We conducted population-based active surveillance for all cases of invasive pneumococcal disease in seven states; plotted annualized weekly rates by geographic location, age, and latitude; and assessed correlations by time-series analysis. In all geographic areas, invasive pneumococcal disease exhibited a distinct winter seasonality, including an increase among children in the fall preceding that for adults and a sharp spike in incidence among adults each year between December 24 and January 7. Pneumococcal disease correlated inversely with temperature (r -0.82 with a 1-week lag; p<0.0001), but paradoxically the coldest states had the lowest rates, and no threshold temperature could be identified. The pattern of disease correlated directly with the sinusoidal variations in photoperiod (r +0.85 with a 5-week lag; p<0.0001). Seemingly unrelated seasonal phenomena were also somewhat correlated. The reproducible seasonal patterns in varied geographic locations are consistent with the hypothesis that nationwide seasonal changes such as photoperiod-dependent variation in host susceptibility may underlie pneumococcal seasonality, but caution is indicated in assigning causality as a result of such correlations.     

Ethnic comparisons of disease severity in children hospitalized with pneumonia in New Zealand

Objective : To determine if there are ethnic differences in disease severity in children hospitalized with pneumonia in New Zealand. Methodology : A population based audit of children hospitalized in Auckland with pneumonia over 12 months from 1 November 1994 to 31 October 1995. The study population was children aged from 0 to 14 years with a discharge diagnosis of pneumonia. The sample was stratified by ethnicity and included 151 Pacific, 85 Mäori and 151 European children. Measurements were made of demographics and prehospital care; vital signs and therapy received in the emergency department and inpatient wards and laboratory investigations performed. Comparisons between the three ethnic groups were adjusted for age, weight, gender, socio‐economic status and relationship with primary care. Results : A larger proportion of Pacific (15%) and Mäori (22%) children than European children (8%) had a respiratory rate elevated for ≥ 2 days, odds ratio (OR) (95% CI): Pacific versus European 2.7 (1.1, 6.8), Mäori versus European 4.3 (1.7, 11.6). A larger proportion of Pacific (15%) and Mäori (15%) children than European children (< 1%) had a heart rate elevated for ≥ 2 days, OR Pacific versus European 17.2 (3.2, 320), Mäori versus European 26.1 (4.4, 508). Compared with European children, a larger proportion of Pacific and Mäori children received intravenous fluids and antibiotics. A larger proportion of Pacific (29%) and Mäori (27%) children than European children (11%) received oxygen for ≥ 2 days, OR Pacific versus European 3.2 (1.6, 6.6), Mäori versus Europeans 2.6 (1.2, 6.2). Conclusions : Based on the comparisons of vital signs and intensity of therapy, Pacific and Mäori children hospitalized with pneumonia have more severe pneumonia than European children.